We have already reported significant elevation of serum granulocyte colony-stimulating factor (G-CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non-repeaters). We examined the clinical data and serum G-CSF levels in 48 patients with acute infections. Serum G-CSF levels were significantly lower in repeaters than in non-repeaters (197.7 +/- 370.0 vs. 1014.1 +/- 924.4 pg/ml. P less than 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non-repeaters (2.87 +/- 0.5 vs. 3.31 +/- 0.4 g/dl. P less than 0.005). It is suggested that administration of recombinant G-CSF may be useful for patients with repeated infections.

Syngeneic SL mice inoculated with murine myeloid leukemia cells (Ml) all died ofleukemia within 30 days. Treatment three times a week with 12.5-50 pmol per mouse of either la,25-dihydroxyvitamin D3 [la,25(OH) It is of great interest that some tumor cell lines also possess similar cytosol receptors to which la,25(OH)2D3 binds specifically (4-6). However, the biological function of la,25(OH)2D3 in tumor cells was not known until quite recently. In 1981, Colston et aL (7) (17,18), the most potent known stimulators in Ml cells, do not induce differentiation of HL-60 cells (13,19).It is known that syngeneic SL mice inoculated with MI cells all die of leukemia (20,21). The marked in vitro effects of la,25(OH)2D3 on cell growth and differentiation (8, 10, 19) led us to examine whether in vivo administration of la,25(OH)2D3 to tumor-bearing mice would decrease their leukemogenicity.In this report, we demonstrate that treatment with either la,25(OH)2D3 or la(OH)D3 considerably prolongs survival times of mice inoculated with Ml cells. MATERIALS AND METHODSAnimals. Inbred SL strain mice were maintained as reported previously (20,21). Six-to eight-week old female mice were used for the experiments. Six-week-old female athymic nude mice with a BALB/c genetic background were supplied by CLEA Japan (Tokyo). They were housed under specific pathogen-free conditions by using Clean Racks (Sanki Kogyo, Tokyo).Inoculation with MI Cells. Ml cells, clone S1 (a clone sensitive to dexamethasone), were maintained as reported (22) 3, 6, 12, 24, or 48 hr later and their blood was collected. The blood plasma Abbreviations: Ml, a murine myeloid leukemia cell line; HL-60, a human myeloid leukemia cell line; la,25(OH)2D3, la,25-dihydroxyvitamin D3; la(OH)D3, la-hydroxyvitamin D3; 25(OH)D3, 25-hydroxyvitamin D3; 24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3.¶ To whom reprint requests should be addressed. 201The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age- matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age- matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

The functional roles of metabotropic glutamate receptor (mGluR) 1 in integrative brain functions were investigated using a potent and selective mGluR1 allosteric antagonist, FTIDC [4-[1-(2-fluoropyridine-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide], in comparison with the mGluR5 allosteric antagonist and the mGluR2/3 orthosteric agonist in rodents. FTIDC reduced maternal separationinduced ultrasonic vocalization and stress-induced hyperthermia without affecting behaviors in the elevated plus maze. An mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and an mGluR2/3 agonist, LY379268 [(1R, 4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid], showed anxiolytic activities in these models, suggesting involvement of postsynaptic mGluR1 in stress-related responses comparable with mGluR5 and mGluR2/3. Analgesic effects of FTIDC were seen in the formalin test but not in the tail immersion test. FTIDC selectively blocked methamphetamineinduced hyperlocomotion and disruption of prepulse inhibition, whereas MPEP and LY379268 did not alter those behaviors, suggesting that pharmacological blockade of mGluR1 could result in antipsychotic-like effects. FTIDC did not elicit catalepsy or impair motor functions at 10 times higher dose than doses showing antipsychotic-like action. In conclusion, blockade of mGluR1 showed antipsychotic-like effects without impairing motor functions, whereas blockade of mGluR5 and activation of mGluR2/3 did not display such activities.L-Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and acts on ionotropic and metabotropic glutamate receptors (mGluRs). The mGluR family consists of eight receptor subtypes, which are divided into three groups based on sequence homology, pharmacological profiles, and signal transduction pathways (De Blasi et al., 2001;Spooren et al., 2003). Group I mGluRs comprise mGluR1 and mGluR5, which are coupled with G q to activate phospholipase C, leading to the release of intracelArticle, publication date, and citation information can be found at